HL-37, a novel anthracene derivative, induces Ca(2+)-mediated apoptosis in human breast cancer cells.
HL-37, a novel anthracene derivative, exhibited potent anticancer activity in many kinds of cancer cells. However, the exact mechanism and signaling pathway involved in HL-37-induced apoptosis have not been fully elucidated. Therefore, we explored the mechanisms of HL-37-mediated apoptosis in MCF-7 and MDA-MB-435 human breast cancer cells. When MCF-7 cells or MDA-MB-435 cells were co-incubated with HL-37, the percentage of apoptotic cell and S phase of cell cycle was markedly increased. In addition, a rise in intracellular calcium levels, ROS production, phosphorylation of JNK and activation of calpain were found in both MCF-7 cells and MDA-MB-435 cells after exposure to HL-37. With the HL-37-mediated reduction of mitochondrial membrane potential, cytochrome c was released from mitochondria to cytosol. Moreover, HL-37 strongly induced cleavage of caspase-4, caspase-9, as well as caspase-3 in MDA-MB-435 cells, whereas, activation of caspase-4, caspase-9 and caspase-7 but not caspase-3 was detected in MCF-7 cells. These results suggested that HL-37 induced MDA-MB-435 and MCF-7 cells apoptosis via oxidative stress and Ca(2+)/calpain/caspase-4 pathway.
Xie
Song-Qiang
SQ
Institute of Pharmacy, Henan University, Kaifeng 475001, China. kfxsq@yahoo.com.cn
Zhang
Zhong-Quan
ZQ
Hu
Guo-Qiang
GQ
Xu
Mei
M
Ji
Bian-Sheng
BS
D000873:Anthracenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects
D000873:Anthracenes; D000970:Antineoplastic Agents; C527615:HL-37 compound